Summary

Adoptive T cell therapy with tumor infiltrating lymphocytes (TIL) has achieved impressive
clinical results with durable complete responses in patients with metastatic melanoma.
Recently, the investigators have completed a pilot study treating 6 patients with metastatic
ovarian cancer. The TILs are isolated from patients own tumor tissue followed by in vitro
expansion and activation for around 4-6 weeks. Before TIL infusion the patients receive 1
week of preconditioning chemotherapy with cyclophosphamide and fludarabine. After TIL
infusion Interleukin-2 is administered to support T cell acitivation and proliferation in
vivo.

The investigators recent pilot study has shown TIL therapy in patients with metastatic
ovarian cancer to be feasible and tolerable. Mainly transient clinical responses where
observed and therefore the investigators plan to combine TIL therapy with checkpoint
inhibitors to potentially increase the clinical effect.

Description

Adoptive T cell therapy with tumor infiltrating lymphocytes (TIL) has achieved impressive
clinical results with durable complete responses in patients with metastatic melanoma.
Recently, the investigators have completed a pilot study treating 6 patients with metastatic
ovarian cancer. The TILs are isolated from patients own tumor tissue followed by in vitro
expansion and activation for around 4-6 weeks. Before TIL infusion the patients receive 1
week of preconditioning chemotherapy with cyclophosphamide and fludarabine. After TIL
infusion Interleukin-2 is administered to support T cell acitivation and proliferation in
vivo.

The investigators recent pilot study has shown TIL therapy in patients with metastatic
ovarian cancer to be feasible and tolerable. Mainly transient clinical responses where
observed and therefore the investigators plan to combine TIL therapy with checkpoint
inhibitors to potentially increase the clinical effect.

Objectives:

To evaluate safety and feasibility when treating patients with metastatic ovarian cancer with
ACT with TILs in combination with checkpoint inhibitors.

Patients will be screened with a physical exam, medical history, blood samples and ECG.

Patients will be treated with one dose of Ipilimumab 14 days before undergoing surgery to
harvest tumor material for TIL production. Patients is admitted on day -8 in order to undergo
lymphodepleting chemotherapy with cyclophosphamide and fludara starting day -7. On day -2
patients will start treatment with Nivolumab every 2 weeks for a total of 4 doses to increase
the activity of the infused TIL product.

On day 0 patients receive TIL infusion and shortly after starts IL-2 stimulation with a daily
subcutaneous dose for a total of 14 days.The patients will followed until progression or up
to 5 years.

Ipilimumab and Nivolumab are novel monoclonal antibodies that have recently been used successfully for treatment of metastatic melanoma. Ipilimumab is a human monoclonal antibody against Cytotoxic T L...

Ipilimumab (Yervoy®) therapy improves outcomes in patients with resected stage III melanoma, and ipilimumab alone or combined with nivolumab (Opdivo®) does so in those with unresectable or metastati...

Ipilimumab is a human monoclonal antibody that targets cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), and it is FDA approved for the treatment of unresectable or metastatic melanoma. Immune-rel...

The randomised phase III clinical trial Checkmate-214 showed a survival superiority for the combination of ipilimumab and nivolumab when compared with the previous standard of care in first-line metas...

New therapeutic strategies including immunotherapy and selective molecular target inhibitors have brought about a new era in the treatment of patients with advanced melanoma. In Japan, the immune chec...

Medical and Biotech [MESH] Definitions

Krukenberg Tumor

Mucocellular carcinoma of the ovary, usually metastatic from the gastrointestinal tract, characterized by areas of mucoid degeneration and the presence of signet-ring-like cells. It accounts for 30%-40% of metastatic cancers to the ovaries and possibly 1%-2% of all malignant ovarian tumors. The lesions may not be discovered until the primary disease is advanced, and most patients die of their disease within a year. In some cases, a primary tumor is not found. (From Dorland, 27th ed; Holland et al., Cancer Medicine, 3d ed, p1685)

Interleukin Receptor Common Gamma Subunit

An interleukin receptor subunit that was originally discovered as a component of the INTERLEUKIN 2 RECEPTOR. It was subsequently found to be a component of several other receptors including the INTERLEUKIN 4 RECEPTOR, the INTERLEUKIN 7 RECEPTOR, the INTERLEUKIN-9 RECEPTOR, the INTERLEUKIN-15 RECEPTOR, and the INTERLEUKIN-21 RECEPTOR. Mutations in the gene for the interleukin common gamma chain have been associated with X-LINKED COMBINED IMMUNODEFICIENCY DISEASES.

Receptors, Interleukin-13

Cell surface receptors for INTERLEUKIN-13. Included under this heading are the INTERLEUKIN-13 RECEPTOR ALPHA2 which is a monomeric receptor and the INTERLEUKIN-4 RECEPTOR TYPE II which has specificity for both INTERLEUKIN-4 and INTERLEUKIN-13.

Interleukin-12 Subunit P40

A cytokine subunit that is a component of both interleukin-12 and interleukin-23. It binds to the INTERLEUKIN-12 SUBUNIT P35 via a disulfide bond to form interleukin-12 and to INTERLEUKIN-23 SUBUNIT P19 to form interleukin-23.

Cyclophosphamide

Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the LIVER to form the active aldophosphamide. It has been used in the treatment of LYMPHOMA and LEUKEMIA. Its side effect, ALOPECIA, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer.

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